title: Activation of aryl hydrocarbon receptor (ahr) by tranilast, an anti-allergy drug, promotes miR-302 expression and cell reprogramming.
abstract: MiR-302 has been shown to regulate pluripotency genes and help somatic cell reprogramming. Thus, promotion of endogenous miR-302 expression could be a desirable way to facilitate cell reprogramming. By using a luciferase reporter system of the miR-302 promoter, we screened and found that an anti-allergy drug, tranilast, could significantly promote miR-302 expression. Further experiments revealed that two aryl hydrocarbon receptor (AhR) binding motifs on the miR-302 promoter are critical and that activation of AhR is required for tranilast-induced miR-302 expression. Consistently, not only tranilast but other AhR agonists promoted miR-302 expression. Furthermore, the activation of AhR facilitated cell reprogramming in a miR-302-dependent way. These results elucidate that miR-302 expression can be regulated by AhR and thus provide a strategy for promoting somatic cell reprogramming by AhR ligands.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Hu
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; D018336:Receptors, Aryl Hydrocarbon; D062367:ortho-Aminobenzoates; C484722:Ahr protein, mouse; C558265:MIRN302 microRNA, mouse; C012293:tranilast
keywords: Aryl Hydrocarbon Receptor; Induced Pluripotent Stem (iPS) Cell; Reprogramming; Small Molecules; Tranilast; microRNA